The Study to Help the AIDS Research Effort (SHARE) started in 1983 when it was funded by the National Institute of Allergy and Infectious Diseases and the National Cancer Institute. From the beginning, the research in Baltimore was closely coordinated with the clinical sites in Pittsburgh, Chicago and Los Angeles. The resulting collaboration between the four clinical sites, investigators at the NIH and the data center became known as the Multicenter AIDS Cohort Study (MACS). The MACS was designed to be a study of the natural history of risk factors for and progression toward AIDS. Shortly after the study began, HIV (known then as HTLV-III/LAV) was discovered, thus making the study a natural history study of HIV infection. Participants have been seen at least every six months since enrollment began in April 1984. An interviewer-administered questionnaire and a focused physical examination have been conducted at each clinical visit. Specimens (including serum, plasma, and cryopreserved peripheral blood mononuclear cells) have been collected at each visit and stored in both national and local repositories. Semen and feces were collected for the first 12 to 30 months of the study, but are now occasionally collected for special studies. The initial cohort in SHARE consisted of 1,153 gay/bisexual men who were recruited from April to October 1984. Of these, 30% were HIV seropositive at baseline and 95 of those who were seronegative at baseline seroconverted. Recruitment was reopened in 1987 in order to recruit lovers of current participants and minority gay men. Two hundred thirty-one more participants were added as of October 1990. Of these, half are African Americans. The prevalence of infection in the newly recruited cohort was 31 % at baseline. From the natural history studies in the MACS, we have learned the risk factors for infection and the natural history of untreated HIV infection. The MACS has contributed significantly to scientific and public health policy decisions in the U.S. Over the last two years the MACS has moved to studying the natural history of treated HIV infection and factors associated with prolonged or shortened survival with HIV infection or clinical AIDS. Followup of cohort members for important outcomes, such as all HIV-related infections, other infections, malignancies, and neuropsychological events, has become a primary focus of the study. Research into the virological and immunopathological mechanisms of progressive HIV infection are vital areas to be addressed in this proposal. A complete description of the clinical spectrum of HIV- associated disorders is also an important area of research for the future. This research will include: epidemiological, nutritional and behavioral factors associated with prolonged survival, and expansion of the neuropsychological studies to accurately describe the natural history of these disorders in HIV infection.